The Opioid Analgesic Reduction Study (OARS) Pilot: A Double-Blind Randomized Multicenter Trial.

BACKGROUND: With addiction rates and opioid deaths increasing, health care providers are obligated to help stem the opioid crisis. As limited studies examine the comparative effectiveness of fixed-dose combination nonopioid analgesia to opioid-containing analgesia, a comparative effectiveness study was planned and refined by conducting a pilot study. METHODS: The Opioid Analgesic Reduction Study (OARS) pilot, a stratified, randomized, multisite, double-blind clinical trial, was designed to test technology and procedures to be used in the full OARS trial. Participants engaged in the full protocol, enabling the collection of OARS outcome data. Eligible participants reporting to 1 of 5 sites for partial or full bony impacted mandibular third molar extraction were stratified by biologic sex and randomized to 1 of 2 treatment groups, OPIOID or NONOPIOID. OPIOID participants were provided 20 doses of hydrocodone 5 mg/acetaminophen 300 mg. NONOPIOID participants were provided 20 doses of ibuprofen 400 mg/acetaminophen 500 mg. OARS outcomes data, including pain experience, adverse effects, sleep quality, pain interference, overall satisfaction, and remaining opioid tablets available for diversion, were collected via surveys, electronic medication bottles, eDiary, and activity/sleep monitor. RESULTS: Fifty-three participants were randomized with 50 completing the OARS pilot protocol. Across all outcome pain domains, in all but 1 time period, NONOPIOID was better in managing pain than OPIOID (P < 0.05 level). Other outcomes suggest less pain interference, less adverse events, better sleep quality, better overall satisfaction, and fewer opioid-containing tablets available for diversion. DISCUSSION: Results suggest patients requiring impacted mandibular third molar extraction would benefit from fixed-dose combination nonopioid analgesia. KNOWLEDGE TRANSFER STATEMENT: Study results suggest fixed-dose nonopioid combination ibuprofen 400 mg/acetaminophen 500 mg is superior to opioid-containing analgesic (hydrocodone 5 mg/acetaminophen 500 mg). This knowledge should inform surgeons and patients in the selection of postsurgical analgesia.

A single-arm pilot of a web-based intervention to improve itch-related quality of life.

BACKGROUND: Many patients with chronic itch and atopic dermatitis (AD) or psoriasis do not receive/use available medical and psychosocial treatments properly due to system, provider and/or patient factors. OBJECTIVE: An educational website (ITCH-RELIEF) to improve itch-related quality of life (QoL) for adults with AD or psoriasis and chronic itch was developed and assessed. ITCH RELIEF stands for Interactive Toolbox of Comprehensive Health Resources to Enhance Living with Itch - Educational Facilitation (for Adults). METHODS: Single-arm pre- and post-test design with 1-month follow-up (N = 137 at baseline). RESULTS: There was statistically and clinically significant improvement in the primary outcome of itch-related QoL impairment as assessed by the ItchyQoL from baseline [M = 78.9, 95% confidence interval (CI) = 75.9, 81.9] to follow up (M = 75.4, CI = 72.4, 78.5), P = 0.007, as well as statistically significant improvement in several itch-related secondary outcomes (all Ps < 0.05). CONCLUSIONS: This study demonstrated initial effectiveness of an online intervention to improve itch-related QoL among individuals with AD or psoriasis and chronic itch. Future studies should address limitations by randomizing more heterogeneous participants, utilizing a longer follow-up and assessing medication use.

[Analysis of factors affecting live birth outcome of frozen-thawed embryo transfer cycle].

Objective: To analyze the related factors affecting the success of frozen-thawed embryo transfer (FET). Methods: A total of 563 couples treated in the Reproductive Medicine Center of Guangdong Hospital of Traditional Chinese Medicine from January 2017 to March 2020 were selected as subjects. A total of 736 FET cycles were included to analyze the live birth outcomes of FET. Pregnancy outcomes, pregnancy complications and embryo status of patients between the live birth group and the non-live birth group were compared. A multivariate logistic regression model was used to evaluate the association between the 15 candidate factors and live birth outcomes for identifying independent factors associated with the live birth outcomes of the FET. Results: Among the enrolled subjects, the men were (33±5) years old at sperm extraction while the women were (31±4) years old at ovum pick-up (OPU) and (32±4) years old at embryo transfer (ET) and their infertility duration were (3.5±2.6) years. There were 333 (45.2%) live birth cycles and 403 (54.8%) non-live birth cycles in the 736 FET cycles. Pregnancy complications occurred in 49 cases (14.7%) of the live birth group. The age of the women at ET ((31±4) vs (32±4) years), the age of the women at OPU ((30±4) vs (32±4) years) and the age of the men at sperm extraction ((33±4) vs (34±5) years) in the live birth group were all lower than those in the non-live birth group. The infertility duration was shorter ((3.2±2.2) vs (3.6±2.8) years), and the proportion of primary infertility was higher ((63.1%, 210 cases) vs (49.6%, 200 cases)) in the live birth group (P<0.05) than those in the non-live birth group. Multivariate logistic regression analyses showed that the age of woman at ET (OR (95%CI): 0.50 (0.27-0.92), P=0.026), the types of infertility (0.62 (0.43-0.88), P=0.008), the numbers of optimal embryos transferred (1.60(1.11-2.31), P=0.012), and the types of embryos transferred (2.43 (1.46-4.01), P=0.001) were statistically significant related factors for live birth outcome of FET. Conclusion: The age of the woman at ET, the types of infertility, the numbers of optimal embryos transferred and the types of embryos transferred are associated factors for the outcomes of live birth after FET.

Occidiofungin is an important component responsible for the antifungal activity of Burkholderia pyrrocinia strain Lyc2.

AIMS: To identify the taxonomy of tobacco rhizosphere-isolated strain Lyc2 and investigate the mechanisms of the antifungal activities, focusing on antimicrobials gene clusters identification and function analysis. METHODS AND RESULTS: Multilocus sequence typing and 16S rRNA analyses indicated that strain Lyc2 belongs to Burkholderia pyrrocinia. Bioassay results indicated strain Lyc2 showed significant antifungal activities against a broad range of plant and animal fungal pathogens and control efficacy on seedling damping off disease of cotton. A 55·2-kb gene cluster which was homologous to ocf gene clusters in Burkholderia contaminans MS14 was confirmed to be responsible for antifungal activities by random mutagenesis; HPLC was used to verify the production of antifungal compounds. Multiple antibiotic and secondary metabolized biosynthesis gene clusters predicated by antiSMASH revealed the broad spectrum of antimicrobials activities of the strain. CONCLUSIONS: Our results revealed the mechanisms of antifungal activities of strain Lyc2 and expand our knowledge about production of occidiofungin in the bacteria Burkholderia. SIGNIFICANCE AND IMPACT OF THE STUDY: Understanding the mechanisms of antifungal activities of strain Lyc2 has contributed to discovery of new antibiotics and expand our knowledge of production of occidiofungin in the bacteria Burkholderia.

Ambient air pollutant concentrations during pregnancy and the risk of fetal growth restriction.

BACKGROUND: Previous studies of air pollution and birth outcomes have not evaluated whether complicated pregnancies might be susceptible to the adverse effects of air pollution. It was hypothesised that trimester mean pollutant concentrations could be associated with fetal growth restriction, with larger risks among complicated pregnancies. METHODS: A multiyear linked birth certificate and maternal/newborn hospital discharge dataset of singleton, term births to mothers residing in New Jersey at the time of birth, who were white (non-Hispanic), African-American (non-Hispanic) or Hispanic was used. Very small for gestational age (VSGA) was defined as a fetal growth ratio <0.75, small for gestational age (SGA) as > or =0.75 and <0.85, and 'reference' births as > or =0.85. Using polytomous logistic regression, associations between mean pollutant concentrations during the first, second and third trimesters and the risks of SGA/VSGA were examined, as well as effect modification of these associations by several pregnancy complications. RESULTS: Significantly increased risk of SGA was associated with first and third trimester PM(2.5) (particulate matter <2.5 microm in aerodynamic diameter), and increased risk of VSGA associated with first, second and third trimester nitrogen dioxide (NO(2)) concentrations. Pregnancies complicated by placental abruption and premature rupture of the membrane had approximately two- to fivefold greater excess risks of SGA/VSGA than pregnancies not complicated by these conditions, although these estimates were not statistically significant. CONCLUSIONS: These findings suggest that ambient air pollution, perhaps specifically traffic emissions during early and late pregnancy and/or factors associated with residence near a roadway during pregnancy, may affect fetal growth. Further, pregnancy complications may increase susceptibility to these effects in late pregnancy.

Lower quit rates among African American and Latino menthol cigarette smokers at a tobacco treatment clinic.

BACKGROUND: Lower rates of smoking cessation and higher rates of lung cancer in African American (AA) smokers may be linked to their preference for mentholated cigarettes. AIM: This study assessed the relationship between menthol smoking, race/ethnicity and smoking cessation among a diverse cohort of 1688 patients attending a specialist smoking cessation service. RESULTS: 46% of the patients smoked mentholated cigarettes, but significantly more AA (81%) and Latino (66%) patients than Whites (32%) smoked menthols. AA and Latino menthol smokers smoked significantly fewer cigarettes per day (CPD) than non-menthol smokers (15.7 vs. 20.3, for AA, and 17.0 vs. 22.1, for Latinos), with no differences among White menthol and non-menthol smokers. At 4-week follow up, AA, Latino and White non-menthol smokers had similar quit rates (54%, 50% and 50% respectively). In contrast, among menthol smokers, AAs and Latinos had lower quit rates (30% and 23% respectively) compared with Whites (43%, p < 0.001). AA and Latino menthol smokers had significantly lower odds of quitting [odds ratio (OR) = 0.34; 95% CI = 0.17, 0.69 for AA, and OR = 0.32; 95% CI = 0.16, 0.62 for Latinos] than their non-menthol counterparts. At 6-month follow up, a similar trend was observed for the race/ethnicity subgroups, with AA menthol smokers having half the odds of being abstinent compared with AA non-menthol smokers (OR = 0.48; 95% CI = 0.25, 0.9). CONCLUSIONS: Despite smoking fewer CPD, AA and Latino menthol smokers experience reduced success in quitting as compared with non-menthol smokers within the same ethnic/racial groups.

First Report of Ear Soft Rot of Corn (Zea mays) Caused by Burkholderia gladioli in the United States.

During the summer of 2005, an uncharacterized disease was observed on sweet corn 'Mirai 301BC' commercially grown in Sunflower County, Mississippi. Initial symptoms developing at the base of the ear on interior husk leaves were brown, water-soaked, irregular lesions. These gradually enlarged up to 10 cm in diameter. Market value was significantly affected when the corn ears had visible symptoms of this disease. Bacterial cell streaming was observed at a magnification of ×675 from the diseased husk. A bacterium was consistently isolated from lesions on nutrient broth yeast (NBY) agar. Colonies on NBY were yellowish white, slightly convex, shiny, and circular with entire margins. Isolates MS102 and MS103, which were chosen for further characterization, were gram negative, lacked arginine dihydrolase, did not produce fluorescent pigment on Pseudomonas F medium, accumulated poly-ß-hydroxybutyrate, and grew aerobically. The isolates were able to utilize l-arabinose, d-mannitol, N-acetylglucosamine, capric acid, malic acid, adipic acid, and phenylacetic acid, but not d-maltose. These characteristics are the same as those described previously for Burkholderia gladioli (3). Analysis of fatty acid methyl ester profiles (Sherlock version TSBA 4.10; Microbial Identification System, Newark, DE) characterized the isolates as B. gladioli (similarity indices: 0.23 to 0.38) and revealed that they have C16:0 3OH, the most characteristic fatty acid for the genus Burkholderia. Confirmation was made by PCR amplification of the nearly complete16S rRNA gene (1,471 bp; GenBank Accession No. EU053154) using universal primers (forward: 5'-AGAGTTTGATCCTGGCTCAG and reverse: 5'-GGCTACCTTGTTACGACTTC). DNA sequence analysis demonstrated that the 16S rRNA gene of the bacterium shared highest identities (99.4 to 99.6%) with that of B. gladioli strains 321gr-6, 223gr-1, and S10 (4). A PCR product (approximately 300 bp) characteristic of B. gladioli also was obtained from both isolates using species-specific primers GLA-f and GLA-r (2). To confirm pathogenicity, cell suspensions (108 CFU/ml in phosphate buffer) of isolates MS102 and MS103 were injected into interior husk leaves of field-grown sweet corn with a 20-gauge needle and syringe (2 ml per ear). Control corn ear husks were injected with phosphate buffer. After 3 days, ear rot symptoms were observed on all plants inoculated with the isolates but not those injected with phosphate buffer. Cell suspension of isolates dropped on nonwounded husks also incited the same symptoms as those inoculated with the syringe. Koch's postulates were fulfilled with reisolation from the inoculated tissues. The identity of the reisolated pathogen was proved by sequencing the 16S rRNA gene. This disease was previously reported in Brazil (1). To our knowledge, this is the first report of B. gladioli causing a disease of corn in the United States. Although the impact of this disease was not observed from 2005 to 2006 because of dry weather and rotation to other crops in the affected field, there is a potential that the bacterium could become established in corn-producing areas as a member of the corn ear rot complex if environmental conditions are favorable. Reference: (1) I. M. G. Almeida et al. Arq. Inst. Biol. Sao Paulo 66:141, 1999. (2) N. Furuya et al. J. Gen. Plant Pathol. 68:220, 2002. (3) M. Gillis et al. Int. J. Syst. Bacteriol. 45:274, 1995. (4) R. Nandakumar et al. Phytopathology (Abstr.) 95(suppl.):S73, 2005.

A physical map of the syringomycin and syringopeptin gene clusters localized to an approximately 145-kb DNA region of Pseudomonas syringae pv. syringae strain B301D.

Genetic and phenotypic mapping of an approximately 145-kb DraI fragment of Pseudomonas syringae pv. syringae strain B301D determined that the syringomycin (syr) and syringopeptin (syp) gene clusters are localized to this fragment. The syr and syp gene clusters encompass approximately 55 kb and approximately 80 kb, respectively. Both phytotoxins are synthesized by a thiotemplate mechanism of biosynthesis, requiring large multienzymatic proteins called peptide synthetases. Genes encoding peptide synthetases were identified within the syr and syp gene clusters, accounting for 90% of the DraI fragment. In addition, genes encoding regulatory and secretion proteins were localized to the DraI fragment. In particular, the salA gene, encoding a regulatory element responsible for syringomycin production and lesion formation in P. syringae pv. syringae strain B728a, was localized to the syr gene cluster. A putative ATP-binding cassette (ABC) transporter homolog was determined to be physically located in the syp gene cluster, but phenotypically affects production of both phytotoxins. Preliminary size estimates of the syr and syp gene clusters indicate that they represent two of the largest nonribosomal peptide synthetase gene clusters. Together, the syr and syp gene clusters encompass approximately 135 kb of DNA and may represent a genomic island in P. syringae pv. syringae that contributes to virulence in plant hosts.

Therapy of X-linked adrenoleukodystrophy: prognosis based upon age and MRI abnormality and plans for placebo-controlled trials.

Evaluation of the therapy of X-linked adrenoleukodystrophy (X-ALD) is hampered by its rarity and by the striking and unpredictable variation in phenotypic expression. We present two approaches that may facilitate therapy evaluation. (1) We have analysed data on 377 X-ALD patients who have been followed at the Kennedy Krieger Institute for a mean period of 38 months and have subdivided them into 18 subgroups on the basis of age and the degree of abnormality in brain magnetic resonance imaging (MRI) as assessed by the Loes score (Am. J. Neuroradrol 1994; 15: 1761). We find that grouping on the basis of age and MRI score provides information that is of significant prognostic value. (2) We present plans for the development of a placebo-controlled multicentre international study that will have sufficient biostatistical power to provide objective evaluation of new therapeutic interventions.

X-Linked adrenoleukodystrophy: overview and prognosis as a function of age and brain magnetic resonance imaging abnormality. A study involving 372 patients.

The phenotypic expression of X-linked adrenoleukodystrophy (X-ALD) ranges from the rapidly progressive childhood cerebral form to the milder adrenomyeloneuropathy (AMN) in adults. It is not possible to predict phenotype by mutation analysis or biochemical assays. This study reports on 372 patients ranging in age from less than 3 years to adulthood, who have been followed at the Kennedy Krieger Institute. With the aim of determining whether a method could be developed to predict clinical course by analysis of data available at time of first contact, the patients were subdivided into 18 subgroups on the basis of age and the extent of brain magnetic resonance (MRI) abnormality utilizing the MRI scoring system devised by Loes et al. Scores to grade degree of neurologic and neuropsychologic impairment were also developed. There was strong correlation between MRI and the neurology and neuropsychology scores at baseline. Information based exclusively on age and MRI score at time of first contact was highly predictive of future clinical course and should aid the evaluation of the effects of bone marrow transplantation and the selection of patients for this procedure, as well as the evaluation of other therapies that may be developed in the future.